• Ischemia
• liver transplantation
• reperfusion injury
• review
• risk factors

• Liver Transplantation/adverse effects
• Humans
• Reperfusion Injury/prevention & control
• Risk Factors
• Syndrome
• Animals

• Humans
• Liver Transplantation/adverse effects
• Reperfusion Injury/diagnosis
• Reperfusion Injury/etiology
• Reperfusion Injury/prevention & control
• Pharmaceutical Preparations
• Postoperative Complications/etiology
• Liver
• Norepinephrine

• RCT
• antioxidant
• antioxidant therapy
• ascorbic acid
• blood
• controlled trials
• hepatic
• ischemia
• ischemic
• liver
• liver transplantation
• postreperfusion syndrome
• randomization
• randomized controlled trial
• reperfusion
• reperfusion injury
• surgery
• surgical
• transplant
• transplantation
• vascular
• vitamin
• vitamin C
• vitamins

• HOPE
• PRS
• hypothermic oxygenated machine perfusion
• liver transplantation
• machine perfusion
• organ preservation
• post-reperfusion syndrome

Liver transplantation (LT) is the curative therapy for decompensated cirrhosis. However, anesthesiologists can find it challenging to manage patients undergoing LT due to the underlying pathologic conditions of patients with end-stage liver disease and the high invasiveness of the procedure, which is frequently accompanied by massive blood loss. Echocardiography is a non-invasive or semi-invasive imaging tool that provides real-time information about the structural and functional status of the heart and is considered to be able to improve outcomes by enabling accurate and detailed assessments. This article reviews the pathophysiologic changes of the heart accompanied by cirrhosis that mainly affect hemodynamics. We also present a comparative review of the diagnostic criteria for cirrhotic cardiomyopathy published by the World Congress of Gastroenterology in 2005 and the Cirrhotic Cardiomyopathy Consortium in 2019. This article discusses the conditions that could affect hemodynamic stability and postoperative outcomes, such as coronary artery disease, left ventricular outflow tract obstruction, portopulmonary hypertension, hepatopulmonary syndrome, pericardial effusion, cardiac tamponade, patent foramen ovale, and ascites. Finally, we cover a number of intraoperative factors that should be considered, including intraoperative blood loss, rapid reaccumulation of ascites, manipulation of the inferior vena cava, post-reperfusion syndrome, and adverse effects of excessive fluid infusion and transfusion. This article aimed to summarize the cardiovascular manifestations of cirrhosis that can affect hemodynamics and can be evaluated using perioperative echocardiography. We hope that this article will provide information about the hemodynamic characteristics of LT recipients and stimulate more active use of perioperative echocardiography.

• Acute kidney injury
• Artificial neural network
• Liver transplantation
• Logistic regression
• Machine learning

• CIT
• MELD score
• PRS
• donor BMI
• donor age
• macrosteatosis

• Consensus
• Fluid Therapy/adverse effects
• Fluid Therapy/mortality
• Hemodynamics
• Humans
• Intraoperative Complications/etiology
• Intraoperative Complications/mortality
• Intraoperative Complications/physiopathology
• Intraoperative Complications/therapy
• Kidney Failure, Chronic/mortality
• Kidney Failure, Chronic/physiopathology
• Kidney Failure, Chronic/surgery
• Liver Transplantation/adverse effects
• Liver Transplantation/mortality
• Risk Assessment
• Risk Factors
• Treatment Outcome

We investigated the impact of postreperfusion syndrome (PRS) on hyperglycemia occurrence and connecting (C) peptide release, which acts as a surrogate marker for insulin resistance, during the intraoperative period after graft reperfusion in patients undergoing living donor liver transplantation (LDLT) using propensity score (PS)-matching analysis.

Medical records from 324 adult patients who underwent elective LDLT were retrospectively reviewed, and their data were analyzed according to PRS occurrence (PRS vs. non-PRS groups) using the PS-matching method. Intraoperative levels of blood glucose and C-peptide were measured through the arterial or venous line at each surgical phase. Hyperglycemia was defined as a peak glucose level >200 mg/dL, and normal plasma concentrations of C-peptide in the fasting state were taken to range between 0.5 and 2.0 ng/mL.

After PS matching, there were no significant differences in pre- and intra-operative recipient findings and donor-graft findings between groups. Although glucose and C-peptide levels continuously increased through the surgical phases in both groups, glucose and C-peptide levels during the neohepatic phase were significantly higher in the PRS group than in the non-PRS group, and larger changes in levels were observed between the preanhepatic and neohepatic phases. There were higher incidences of C-peptide levels >2.0 ng/mL and peak glucose levels >200 mg/dL in the neohepatic phase in patients with PRS than in those without. PRS adjusted for PS with or without exogenous insulin infusion was significantly associated with hyperglycemia occurrence during the neohepatic phase.

Elucidating the association between PRS and hyperglycemia occurrence will help with establishing a standard protocol for intraoperative glycemic control in patients undergoing LDLT.

• Coronary artery disease
• Orthotopic liver transplantation
• Post-reperfusion syndrome

The DIAMOND study of de novo liver transplant patients showed that prolonged-release tacrolimus exposure in the acute post-transplant period maintained renal function over 24 weeks of treatment. To assess these findings further, we performed a post-hoc analysis in patients according to baseline kidney function, Model for End-stage Liver Disease [MELD] scores, and donor age.

Patients received prolonged-release tacrolimus (initial-dose, Arm 1: 0.2 mg/kg/day, Arm 2: 0.15–0.175 mg/kg/day, Arm 3: 0.2 mg/kg/day delayed until Day 5), mycophenolate mofetil and 1 steroid bolus. Arms 2 and 3 also received basiliximab. The recommended tacrolimus target trough levels to Day 42 post-transplantation were 5–15 ng/mL in all arms. In this post-hoc analysis, change in renal outcome, based on estimated glomerular filtration rate (eGFR), Modified Diet in Renal Disease-4 (MDRD4), values from baseline to Week 24 post-transplantation, were assessed according to baseline patient factors: eGFR (≥60 and <60 mL/min/1.73 m²), MELD score (<25 and ≥25) and donor age (<50 and ≥50 years).

Baseline characteristics were comparable (Arms 1–3: n=283, n=287, n=274, respectively). Patients with baseline renal function, eGFR ≥60 mL/min/1.73 m², experienced a decrease in eGFR in all tacrolimus treatment arms. In patients with lower baseline renal function (eGFR <60 mL/min/1.73 m²), an advantage for renal function was observed with both the early lower-dose and delayed higher-dose tacrolimus regimens compared with the early introduction of higher-dose tacrolimus. At Week 24, renal function was higher in the early-lower tacrolimus arm with older donors, and the delayed higher-dose tacrolimus arm with younger donors, both compared with early higher-dose tacrolimus.

Pre-transplantation factors, such as renal function and donor age, could guide the choice of prolonged-release tacrolimus regimen following liver transplantation.

• Donation after cardiac death
• Extended criteria donors
• Graft preservation solutions
• Hypothermic machine perfusion
• Ischemia-reperfusion injury
• Liver graft preservation
• Marginal grafts
• Normothermic machine perfusion
• Static cold storage
• Transplant complications

Postreperfusion syndrome (PRS) is a dreadful and well-documented complication in adult liver transplantation (LT). However, information regarding PRS in pediatric LT is still scarce. We aimed to identify the incidence, risk factors and associated outcomes of pediatric LT in a single-center study.

The medical records of 75 consecutive pediatric patients who underwent deceased donor liver transplantation (DDLT) from July 2015 to October 2017 were retrospectively reviewed. PRS was determined according to the Peking criteria when significant arrhythmia or refractory hypotension occurred following revascularization of the liver graft. Patients were divided into PRS and non-PRS groups. Preoperative, intraoperative, and postoperative data were collected and compared between the 2 groups. Independent risk factors for PRS were analyzed using binary logistic regression analysis.

PRS occurred in 26 patients (34.7%). Univariate analysis showed that the graft-to-recipient weight ratio (P=0.023), donor warm ischemia time (P<0.001), and the use of an expanded criteria donor (ECD) liver graft (P<0.001) were significant predictors of PRS. Binary logistic regression showed that the use of an ECD liver graft (odds ratio [OR]: 18.668; 95% confidence interval [95% CI]: 4.866–71.622) and lower hematocrit (HCT) level before reperfusion (OR: 0.878; 95% CI: 0.782–0.985) were independent predictors of PRS. PRS was significantly associated with early allograft dysfunction (73.1% vs. 18.4%, P<0.001), primary nonfunction (11.5% vs. 0.0%, P=0.039), and a prolonged hospital stay (median: 30.5 vs. 21.0, P=0.007).

The use of an ECD liver graft and lower HCT level before reperfusion were independent risk factors for PRS in pediatric DDLT. Intraoperative PRS occurrence seems to be associated with poor liver allograft function and worsened patient postoperative outcomes.

The discrepancy between demand and supply for liver transplants (LT) has led to an increased transplantation of organs from extended criteria donors (ECD).

In this single center retrospective analysis of 122 cadaveric LT recipients, we investigated predictors of postreperfusion syndrome (PRS) including transplant liver quality categorized by both histological assessment of steatosis and subjective visual assessment by the transplanting surgeon using multivariable regression analysis. Furthermore, we describe the relevance of PRS during the intraoperative and postoperative course of LT recipients.

53.3% (n = 65) of the patients suffered from PRS. Risk factors for PRS were visually assessed organ quality of the liver grafts (acceptable: OR 12.2 [95% CI 2.43–61.59], P = 0.002; poor: OR 13.4 [95% CI 1.48–121.1], P = 0.02) as well as intraoperative norepinephrine dosage before reperfusion (OR 2.2 [95% CI 1.26–3.86] per 0.1 μg kg^− 1 min^− 1, P = 0.01). In contrast, histological assessment of the graft was not associated with PRS. LT recipients suffering from PRS were hemodynamically more instable after reperfusion compared to recipients not suffering from PRS. They had lower mean arterial pressures until the end of surgery (P < 0.001), received more epinephrine and norepinephrine before reperfusion (P = 0.02 and P < 0.001, respectively) as well as higher rates of continuous infusion of norepinephrine (P < 0.001) and vasopressin (P = 0.02) after reperfusion. Postoperative peak AST was significantly higher (P = 0.001) in LT recipients with PRS. LT recipients with intraoperative PRS had more postoperative adverse cardiac events (P = 0.05) and suffered more often from postoperative delirium (P = 0.04).

Patients receiving ECD liver grafts are especially prone to PRS. Anesthesiologists should keep these newly described risk factors in mind when preparing for reperfusion in patients receiving high-risk organs.

• Cold ischemia time
• Hyponatremia
• Steatosis

Predicting the occurrence of severe postreperfusion syndrome (PRS) is clinically challenging. We investigated whether the flushed fluid potassium concentration (FFK) was associated with severe PRS in deceased donor liver transplantation (DDLT).

Forty adult DDLT recipients were enrolled in this retrospective study. Effluent solution samples were collected at the end of the portal vein flush, and the FFK was determined using a point-of-care blood gas analyzer. The risk factors associated with severe PRS and the clinical outcomes in 2 groups were compared.

Severe PRS occurred in 22 out of 40 patients (55.0%). The FFK of the severe PRS group was significantly higher than that of the non-severe PRS group (median, 9.6 vs. 5.8, P<0.001). Other variables associated with severe PRS included the donor risk index (DRI), Child-Turcotte-Pugh score, donor type, donor warm ischemia time, and Model for End-stage Liver Disease score. The area under the receiver operator characteristic curve for the FFK was 0.982, and the best cut-off value of the FFK for predicting severe PRS was 6.75 mmol/L (100.0% sensitivity and 88.9% specificity). A significant positive correlation was observed between the FFK and DRI (R=0.714). Patients who experienced severe PRS had a higher early allograft dysfunction rate (63.6% vs. 22.2%, P=0.019) and a longer hospital stay (median, 33.0 vs. 24.0, P=0.034).

Both the severity of the recipient’s liver disease and the donor graft factors play an important role in the development of severe PRS in DDLT. An FFK of more than 6.75 mmol/L was associated with severe PRS after reperfusion.

• graft flushing
• graft rinse
• ischemia/reperfusion injury
• postreperfusion syndrome
• preservative solution

This review aims at evaluating the existing evidence regarding post reperfusion syndrome, providing a description of the pathophysiologic mechanisms involved and possible management and preventive strategies. A PubMed search was conducted using the MeSH database, “Reperfusion” AND “liver transplantation” were the combined MeSH headings; EMBASE and the Cochrane library were also searched using the same terms. 52 relevant studies and one ongoing trial were found. The concept of post reperfusion syndrome has evolved through years to a multisystemic disorder. The implications of the main organ, recipient and procedure related factors in the genesis of this complex syndrome are discussed in the text as the novel pharmacologic and technical approaches to reduce its incidence. However the available evidence about risk factors, physiopathology and preventive measures is still confusing, the presence of two main definitions and the numerosity of possible confounding factors greatly complicates the interpretation of the studies.

• Liver transplantation
• Reperfusion
• Ischemia-reperfusion injury
• Hemodynamics
• Drug therapy

• Animals
• Hemodynamics
• Humans
• Liver Circulation
• Liver Transplantation/adverse effects
• Models, Animal
• Reperfusion Injury/etiology
• Reperfusion Injury/physiopathology
• Reperfusion Injury/prevention & control
• Risk Factors
• Treatment Outcome

As surgical and graft preservation techniques have improved and immunosuppressive drugs have advanced, liver transplantation (LT) is now considered the gold standard for treating patients with end-stage liver disease worldwide. However, despite the improved survival following LT, severe hemodynamic disturbances during LT remain a serious issue for the anesthesiologist. The greatest hemodynamic disturbance is postreperfusion syndrome (PRS), which occurs at reperfusion of the donated liver after unclamping of the portal vein. PRS is characterized by marked decreases in mean arterial pressure and systemic vascular resistance, and moderate increases in pulmonary arterial pressure and central venous pressure. The underlying pathophysiological mechanisms of PRS are complex. Moreover, risk factors associated with PRS are not fully understood. Rapid and appropriate treatment with vasopressors, volume replacement, or venesection must be provided depending on the cause of the hemodynamic disturbance when hemodynamic instability becomes profound after reperfusion. The negative effects of PRS on postoperative early morbidity and mortality are clear, but the effect of PRS on postoperative long-term mortality remains a matter of debate.

• Hemodynamic disturbance
• Liver transplantation
• Reperfusion

• liver transplantation
• cardiac function
• postreperfusion syndrome

• Adolescent
• Adult
• Aged
• Arterial Pressure
• Cytokines/blood
• Echocardiography, Doppler, Color/methods
• Echocardiography, Transesophageal/methods
• Female
• Humans
• Liver Transplantation/methods
• Male
• Middle Aged
• Prospective Studies
• Ventricular Function/physiology
• Young Adult

• Aminocaproic Acid/pharmacology
• Double-Blind Method
• Hemodynamics/drug effects
• Humans
• Liver/blood supply
• Liver/drug effects
• Liver/metabolism
• Liver Transplantation
• Middle Aged
• Protein C/metabolism

• cardiomyopathy
• cardiovascular complications
• cirrhosis
• heart failure
• liver transplant

• Hemodialysis
• liver transplantation
• outcomes
• pretransplant renal failure
• renal disease in liver transplantation